title: DNA supercoiling enhances cooperativity and efficiency of an epigenetic switch.
abstract: Bacteriophage λ stably maintains its dormant prophage state but efficiently enters lytic development in response to DNA damage. The mediator of these processes is the λ repressor protein, CI, and its interactions with λ operator DNA. This λ switch is a model on the basis of which epigenetic switch regulation is understood. Using single molecule analysis, we directly examined the stability of the CI-operator structure in its natural, supercoiled state. We marked positions adjacent to the λ operators with peptide nucleic acids and monitored their movement by tethered particle tracking. Compared with relaxed DNA, the presence of supercoils greatly enhances juxtaposition probability. Also, the efficiency and cooperativity of the λ switch is significantly increased in the supercoiled system compared with a linear assay, increasing the Hill coefficient.
authors.affiliation: The Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Kamilla
authors.initials: K
authors.lastname: Norregaard
authors.forename: Magnus
authors.initials: M
authors.lastname: Andersson
authors.forename: Kim
authors.initials: K
authors.lastname: Sneppen
authors.forename: Peter Eigil
authors.initials: PE
authors.lastname: Nielsen
authors.forename: Stanley
authors.initials: S
authors.lastname: Brown
authors.forename: Lene B
authors.initials: LB
authors.lastname: Oddershede
mesh_terms: D000465:Algorithms; D010582:Bacteriophage lambda / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D004278:DNA, Superhelical / Q000235:genetics* / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D008242:Lysogeny / Q000235:genetics; D008957:Models, Genetic; D009875:Operator Regions, Genetic / Q000235:genetics; D039002:Prophages / Q000235:genetics*; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism; D014775:Virus Activation / Q000235:genetics*
chemical_list: D004278:DNA, Superhelical; D004279:DNA, Viral; D012097:Repressor Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins
keywords: autoregulation; epigentic switch; gene regulation; kinetics; repression